Deciphering the impact of ectopic SNAI1 expression on renal tubular cell proteome and functions
Ontology highlight
ABSTRACT: Snail1 is crucial in regulating epithelial mesenchymal transition (EMT), which leads to excessive extracellular matrix (ECM) production and organ fibrosis including the kidney. Elucidating the roles of snail1 in EMT and kidney fibrosis is thus vital for developing targeted therapies. This study investigated the alterations in the proteome of SNAI1-overexpressed proximal tubular epithelial cells over the vector-transfected cells by label-free quantitative proteomics. Of 670 identified proteins, 233 showed significant changes due to ectopic snail1 expression. Of these, immunoblotting confirmed the decreased HSP60 and HSP70 while increased DDX1. X2K Appyter predicted the top ten transcription factors as key upstream regulators of the altered proteome. KEGG enrichment analysis revealed that these altered proteins were primarily associated with translational regulation, ribosome, cell cycle regulation, and cellular senescence. GO enrichment showed that focal adhesion, the structure where cells maintain cell interior-ECM interactions, was markedly overrepresented. Accordingly, functional validations demonstrated that SNAI1-overexpressed cells displayed aberrant ribosome biogenesis, indicated by increasing nucleophosmin and the nucleolar organizer regions. SNAI1-overexpressed cells exhibited senescent phenotypes including cell enlargement and increased granularity, up-regulated senescent makers p21 and γH2AX, and enhanced MMP-9 secretion. Moreover, SNAI1-overexpressed cells up-regulated paxillin, a scaffold protein located at focal adhesions crucial for their dynamic regulation. These findings provide insights into the molecular processes governed by snail1 during renal tubular cells undergoing EMT.
INSTRUMENT(S):
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Epithelial Cell, Kidney
DISEASE(S): Renal Fibrosis
SUBMITTER:
Visith Thongboonkerd
LAB HEAD: Prof. Visith Thongboonkerd
PROVIDER: PXD061033 | Pride | 2026-04-27
REPOSITORIES: Pride
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